Field of Invention
The present disclosure relates to a sensing device, a sensing system and a sensing method for biofunctionalized nanoslits combined with fluorescence microscopy for ultra-fast sensing kinetics studies of labeled molecules but with simple/low-cost setup.
Related Art
Kinetic monitoring of protein interactions offers fundamental insights of their cellular functions and is a vital key in developing potential diagnostic test and bio-therapeutic treatment. Surface plasmon resonance (SPR) and quartz crystal microbalance (QCM) are currently standard commercialized technology routinely used in the field of pharmaceutical and life sciences, offering a real-time detection of biomolecular interactions without label requirement. However, these techniques require high-cost dedicated sensor surface and integration of optical or mechanical components which in turn increases overall assay costs and complicate the instrument setup.
More specifically, surface plasmon resonance (SPR) requires high-cost sensor surface and sophisticated setup. SPR lacks spatial resolution and is expensive/complicated to implement, has low sensitivity (˜nM), much (˜1000×) higher amount of reagent consumption (10 μL), low multiplexing capability, high SPR chip cost (˜$300/chip). QCM (Quartz crystal microbalance) has no spatial resolution and has low sensitivity. Moreover, QCM has no multiplexing capability and requires higher amount of reagent consumption and high chip cost (˜$100/chip).
TIRFM (total internal reflection fluorescence microscopy) requires complicated apparatus, higher amount of reagent consumption. Integrated bioelectronics sensors involve complicated fabrication processes or electronics.
The typical platforms described above have low sensitivity (nM range) and are not suitable for small amount of sample consumption.
The time it takes to detect specific biomolecules in a sample is mainly limited by the detector sensitivity and the time it takes for the lowest number of molecules that can be detected to reach the sensor. While a wide range of very sensitive devices is now available (electrochemical sensors, optical sensors . . . ), when working with small sensing areas and low-concentration samples, the diffusion time is the main limiting factor for most microfluidic sensing platforms. Thus, overcoming diffusion is now mandatory in order to achieve ultra-fast detection. Technical solutions used in micro-total analysis systems, or microTAS, and microarray technologies consist in using convection and reciprocating flow in microchannels or nanochannels, in mixing the solution, and in locally increasing the concentration of biomolecules e.g. via dielectrophoresis. Though detection time can be reduced from several hours to several minutes using these methods, the main drawback of most of these methods is that they can be challenging to implement with highly complex manufacturing process.